C-reactive protein concentrations diverge as a function of substance use disorder: A pre-registered replication in a clinical sample.

BACKGROUND: Inflammatory biomarkers may differentiate clinical disorders, which could lead to more targeted interventions. Analyses within a clinical sample (May et al., 2021) revealed that females with substance use disorders (SUD) exhibited lower C-reactive protein (CRP) and higher interleukin (IL)-8 and -10 concentrations than females without SUD who met criteria for mood/anxiety disorders. We aimed to replicate these findings in a new sample. METHODS: Hypotheses and analyses were preregistered. Treatment-seeking individuals with mood/anxiety disorders and/or SUD (N = 184) completed a blood draw, clinical interview, and questionnaires. Participants were categorized as SUD+ (45F, 43M) and SUD- (78F, 18M). Principal component analysis (PCA) of questionnaire data resulted in two factors reflecting appetitive and aversive emotional states. SUD group and nuisance covariates (PCA factors, age, body mass index [BMI], medication, nicotine [and hormones in females]) predicted biomarker concentrations (CRP, IL-8, and IL-10) in regressions. RESULTS: In females, the omnibus CRP model [F(8, 114) = 8.02, p <.001, R²-adjusted =.32] indicated that SUD+ exhibited lower CRP concentrations than SUD- (ß = -.33, t = -3.09, p =.002, 95% CI [-.54, -.12]) and greater BMI was associated with higher CRP levels (ß =.58, t = 7.17, p <.001, 95% CI [.42,.74]). SUD+ exhibited higher IL-8 levels than SUD- in simple but not omnibus regression models. CONCLUSION: Findings across two samples bolster confidence that females with SUD show attenuated CRP-indexed inflammation. As SUD+ comorbidity was high, replication is warranted with respect to specific SUD classes (i.e., stimulants versus cannabis).

Rumination and Over-Recruitment of Cognitive Control Circuits in Depression.

BACKGROUND: Rumination is associated with greater cognitive dysfunction and treatment resistance in major depressive disorder (MDD), yet its underlying neural mechanisms are not well understood. Since rumination is characterized by difficulty in controlling negative thoughts, the present study investigated whether rumination is associated with aberrant cognitive control in the absence of negative emotional information. METHODS: Individuals with MDD (n=176) and healthy volunteers (n=52) completed the Stop Signal Task with varied stop signal difficulty during functional magnetic resonance imaging. In the task, a longer stop signal asynchrony made stopping difficult (Hard-stop) while a shorter stop signal asynchrony allowed more time for stopping (Easy-stop). RESULTS: In MDD participants, higher rumination intensity was associated with greater neural activity in response to difficult inhibitory control in the frontoparietal regions. Greater activation for difficult inhibitory control associated with rumination was also positively related to state fear. The imaging results provide compelling evidence for the neural basis of inhibitory control difficulties in MDD individuals with high rumination. CONCLUSIONS: The association between higher rumination intensity and greater neural activity in regions involved in difficult inhibitory control tasks may provide treatment targets for interventions aimed at improving inhibitory control and reducing rumination in this population.

Digital Media and Developing Brains: Concerns and Opportunities.

Purpose of Review: The incorporation of digital technologies and their use in youth's everyday lives has been increasing rapidly over the past several decades with possible impacts on youth development and mental health. This narrative review aimed to consider how the use of digital technologies may be influencing brain development underlying adaptive and maladaptive screen-related behaviors. Recent Findings: To explore and provide direction for further scientific inquiry, an international group of experts considered what is known, important gaps in knowledge, and how a research agenda might be pursued regarding relationships between screen media activity and neurodevelopment from infancy through childhood and adolescence. While an understanding of brain-behavior relationships involving screen media activity has been emerging, significant gaps exist that have important implications for the health of developing youth. Summary: Specific considerations regarding brain-behavior relationships involving screen media activity exist for infancy, toddlerhood, and early childhood; middle childhood; and adolescence. Transdiagnostic frameworks may provide a foundation for guiding future research efforts. Translating knowledge gained into better interventions and policy to promote healthy development is important in a rapidly changing digital technology environment.

Screen time, sleep, brain structural neurobiology, and sequential associations with child and adolescent psychopathology: Insights from the ABCD study.

Background and Aims: The precise roles of screen media activity (SMA) and sleep problems in relation to child/adolescent psychopathology remain ambiguous. We investigated temporal relationships among sleep problems, SMA, and psychopathology and potential involvement of thalamus-prefrontal-cortex (PFC)-brainstem structural covariation. Methods: This study utilized data from the Adolescent Brain Cognitive Development study (n = 4,641 ages 9-12) at baseline, Year1, and Year2 follow-up. Cross-Lagged Panel Models (CLPMs) investigated reciprocal predictive relationships between sleep duration/problems, SMA, and psychopathology symptoms. A potential mediating role of baseline Thalamus-PFC-brainstem covariation on SMA-externalizing relationships was examined. Results: Participants were divided into discovery (n = 2,359, 1,054 girls) and replication (n = 2,282, 997 girls) sets. CLPMs showed 1) bidirectional associations between sleep duration and SMA in late childhood, with higher frequency SMA predicting shorter sleep duration (ß = -0.10 [95%CI: -0.16, -0.03], p = 0.004) and vice versa (ß = -0.11 [95%CI: -0.18, -0.05], p < 0.001); 2) externalizing symptoms at age 10-11 predicting sleep problems (ß = 0.11 [95%CI: 0.04, 0.19], p = 0.002), SMA (ß = 0.07 [95%CI: 0.01, 0.13], p = 0.014), and internalizing symptoms (ß = 0.09 [95%CI: 0.05, 0.13], p < 0.001) at age 11-12; and 3) externalizing behavior at age 10-11 partially mediating the relationship between baseline thalamus-PFC-brainstem covariation and SMA at age 11-12 (indirect effect = 0.032 [95%CI: 0.003, 0.067], p-value = 0.030). Findings were replicable. Conclusion: We found bi-directional SMA-sleep-duration associations in late childhood. Externalizing symptoms preceded future SMA and sleep disturbances and partially mediated relationships between structural brain covariation and SMA. The findings emphasize the need for understanding individual differences and developing and implementing integrated strategies addressing both sleep concerns and screen time to mitigate potential impacts on psychopathology.

Leptin's Inverse Association with Brain Morphology and Depressive Symptoms - A Discovery and Confirmatory Study Across Two Independent Samples.

BACKGROUND: Major Depressive Disorder (MDD) has a complex, bi-directional relationship with metabolic dysfunction, yet the neural correlates of this association are not well understood. METHOD: In this cross-sectional investigation, we employed a two-step 'discovery and confirmatory' strategy, utilizing two independent samples (Sample 1: 288 participants, Sample 2: 196 participants) to examine the association between circulating indicators of metabolic health (leptin and adiponectin) and brain structures in individuals with MDD. RESULTS: We found a replicable inverse correlation between leptin levels and cortical surface area within essential brain areas responsible for emotion regulation, such as the left posterior cingulate cortex, right pars orbitalis, right superior temporal gyrus, and right insula (standardized beta coefficient (SBC) ranged: -0.27 to -0.49, puncorrected <0.05). Notably, this relationship was independent of C-Reactive Protein levels. We also identified a significant interaction effect of leptin levels and diagnosis on the cortical surface area of the right superior temporal gyrus (SBC = 0.26 in sample 1, SBC = 0.30 in sample 2, puncorrected < 0.05). We also observed a positive correlation between leptin levels and atypical depressive symptoms in both MDD groups (r = 0.14 in sample 1, r = 0.29 in sample 2, puncorrected < 0.05). CONCLUSION: The inverse association between leptin and cortical surface area in brain regions that are important for emotion processing and leptin's association with sleep disturbances supports the hypothesis that metabolic processes may be related to emotion regulation. However, the molecular mechanisms through which leptin might exert these effects should be explored further.

Voxel-wise multivariate analysis of brain-psychosocial associations in adolescents reveals six latent dimensions of cognition and psychopathology.

BACKGROUND: Adolescence heralds the onset of much psychopathology, which may be conceptualized as an emergence of altered covariation between symptoms and brain measures. Multivariate methods can detect such modes of covariation or latent dimensions, but none specifically relating to psychopathology have yet been found using population-level structural brain data. Using voxel-wise (instead of parcellated) brain data may strengthen latent dimensions' brain-psychosocial relationships, but this creates computational challenges. METHODS: We obtained voxel-wise grey matter density and psychosocial variables from the baseline (aged 9-10 years) Adolescent Brain and Cognitive Development cohort (n=11288), and employed a state-of-the-art segmentation method, sparse partial least squares, and a rigorous machine learning framework to prevent overfitting. RESULTS: We found six latent dimensions, four pertaining specifically to mental health. The mental health dimensions related to overeating, anorexia/internalizing, oppositional symptoms (all p<0.002) and ADHD symptoms (p=0.03). ADHD related to increased and internalizing related to decreased grey matter density in dopaminergic and serotonergic midbrain areas, whereas oppositional symptoms related to increased grey matter in a noradrenergic nucleus. Internalizing related to increased and oppositional symptoms to reduced grey matter density in insula, cingulate and auditory cortices. Striatal regions featured strongly, with reduced caudate nucleus grey matter in ADHD, and reduced putamen grey matter in oppositional/conduct problems. Voxel-wise grey matter density generated stronger brain-psychosocial correlations than brain parcellations. CONCLUSIONS: Voxel-wise brain data strengthen latent dimensions of brain-psychosocial covariation and sparse multivariate methods increase their psychopathological specificity. Internalizing and externalizing are associated with opposite grey matter changes in similar cortical and subcortical areas.

Medication Use is Associated with Distinct Microbial Features in Anxiety and Depression.

This study investigated the relationship between gut microbiota and neuropsychiatric disorders (NPDs), specifically anxiety disorder (ANXD) and/or major depressive disorder (MDD), as defined by DSM-IV or V criteria. The study also examined the influence of medication use, particularly antidepressants and/or anxiolytics, classified through the Anatomical Therapeutic Chemical (ATC) Classification System, on the gut microbiota. Both 16S rRNA gene amplicon sequencing and shallow shotgun sequencing were performed on DNA extracted from 666 fecal samples from the Tulsa-1000 and NeuroMAP CoBRE cohorts. The results highlight the significant influence of medication use; antidepressant use is associated with significant differences in gut microbiota beta diversity and has a larger effect size than NPD diagnosis. Next, specific microbes were associated with ANXD and MDD, highlighting their potential for non-pharmacological intervention. Finally, the study demonstrated the capability of Random Forest classifiers to predict diagnoses of NPD and medication use from microbial profiles, suggesting a promising direction for the use of gut microbiota as biomarkers for NPD. The findings suggest that future research on the gut microbiota's role in NPD and its interactions with pharmacological treatments are needed.

Exploring the role of neuronal-enriched extracellular vesicle miR-93 and interoception in major depressive disorder.

Major depressive disorder (MDD) is associated with interoceptive processing dysfunctions, but the molecular mechanisms underlying this dysfunction are poorly understood. This study combined brain neuronal-enriched extracellular vesicle (NEEV) technology and serum markers of inflammation and metabolism with Functional Magnetic Resonance Imaging (fMRI) to identify the contribution of gene regulatory pathways, in particular micro-RNA (miR) 93, to interoceptive dysfunction in MDD. Individuals with MDD (n = 41) and healthy comparisons (HC; n = 35) provided blood samples and completed an interoceptive attention task during fMRI. EVs were separated from plasma using a precipitation method. NEEVs were enriched by magnetic streptavidin bead immunocapture utilizing a neural adhesion marker (L1CAM/CD171) biotinylated antibody. The origin of NEEVs was validated with two other neuronal markers - neuronal cell adhesion molecule (NCAM) and ATPase Na+/K+ transporting subunit alpha 3 (ATP1A3). NEEV specificities were confirmed by flow cytometry, western blot, particle size analyzer, and transmission electron microscopy. NEEV small RNAs were purified and sequenced. Results showed that: (1) MDD exhibited lower NEEV miR-93 expression than HC; (2) within MDD but not HC, those individuals with the lowest NEEV miR-93 expression had the highest serum concentrations of interleukin (IL)-1 receptor antagonist, IL-6, tumor necrosis factor, and leptin; and (3) within HC but not MDD, those participants with the highest miR-93 expression showed the strongest bilateral dorsal mid-insula activation during interoceptive versus exteroceptive attention. Since miR-93 is regulated by stress and affects epigenetic modulation by chromatin re-organization, these results suggest that healthy individuals but not MDD participants show an adaptive epigenetic regulation of insular function during interoceptive processing. Future investigations will need to delineate how specific internal and external environmental conditions contribute to miR-93 expression in MDD and what molecular mechanisms alter brain responsivity to body-relevant signals.

Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity: A Systematic Review.

Importance: In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers. Objective: To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts. Evidence Review: The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders. Findings: There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes. Conclusions and Relevance: Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.

Heartbeat-evoked neural response abnormalities in generalized anxiety disorder during peripheral adrenergic stimulation.

Hyperarousal symptoms in generalized anxiety disorder (GAD) are often incongruent with the observed physiological state, suggesting that abnormal processing of interoceptive signals is a characteristic feature of the disorder. To examine the neural mechanisms underlying interoceptive dysfunction in GAD, we evaluated whether adrenergic modulation of cardiovascular signaling differentially affects the heartbeat-evoked potential (HEP), an electrophysiological marker of cardiac interoception, during concurrent electroencephalogram and functional magnetic resonance imaging (EEG-fMRI) scanning. Intravenous infusions of the peripheral adrenergic agonist isoproterenol (0.5 and 2.0 micrograms, µg) were administered in a randomized, double-blinded and placebo-controlled fashion to dynamically perturb the cardiovascular system while recording the associated EEG-fMRI responses. During the 0.5 µg isoproterenol infusion, the GAD group (n = 24) exhibited significantly larger changes in HEP amplitude in an opposite direction than the healthy comparison (HC) group (n = 24). In addition, the GAD group showed significantly larger absolute HEP amplitudes than the HC group during saline infusions, when cardiovascular tone did not increase. No significant group differences in HEP amplitude were identified during the 2.0 µg isoproterenol infusion. Using analyzable blood oxygenation level-dependent fMRI data from participants with concurrent EEG-fMRI data (21 GAD and 21 HC), we found that the aforementioned HEP effects were uncorrelated with fMRI signals in the insula, ventromedial prefrontal cortex, dorsal anterior cingulate cortex, amygdala, and somatosensory cortex, brain regions implicated in cardiac signal processing in prior fMRI studies. These findings provide additional evidence of dysfunctional cardiac interoception in GAD and identify neural processes at the electrophysiological level that may be independent from blood oxygen level-dependent responses during peripheral adrenergic stimulation.

Amphetamine use disorder is associated with striatum hypoactivation during anticipation of loss and reward.

BACKGROUND: Dysregulated ventral striatum function has been proposed as one important process occurring in individuals with substance use disorder. This study investigates the role of altered reward and loss anticipation, which is an important component of impaired decision-making, impulsivity, and vulnerability to relapse in individuals with amphetamine use disorder (AMP). AIMS: To determine whether AMP is associated with blunted striatum, prefrontal cortex, and insula signals during win and loss anticipation. METHODS: Participants with and without AMP (AMP+ n = 46, AMP- n = 90) from the Tulsa 1000 study completed a monetary incentive delay (MID) task during functional magnetic resonance imaging. RESULTS: Group main effects indicated that: (1) AMP+ exhibited lower bilateral caudate/putamen and left nucleus accumbens signal than AMP- across anticipation of wins and losses; and (2) AMP+ showed slower reaction times than AMP- during loss anticipation. Group*condition interactions demonstrated that AMP+ exhibited greater right amygdala signal than AMP- while anticipating large wins, a pattern that reversed when anticipating small losses. Left caudate/putamen attenuations in AMP+ during small loss anticipation were also evident. Groups did not differ in prefrontal or insula signals. CONCLUSIONS: AMP+ individuals have altered neural processing and response patterns during reward and loss anticipation, potentially reflecting impairments in dopamine function, which may influence their decision-making and reactions to different win/loss scenarios. These findings help to explain why AMP+ have difficulty with decision-making and exhibit a heightened focus on immediate rewards or punishments.

Managerial and Organizational Challenges in the Age of AI.

This Viewpoint discusses the managerial and organizational challenges that could result from the use of artificial intelligence systems in psychiatric research and care.

Out of control: computational dynamic control dysfunction in stress- and anxiety-related disorders.

Control theory, which has played a central role in technological progress over the last 150 years, has also yielded critical insights into biology and neuroscience. Recently, there has been a surging interest in integrating control theory with computational psychiatry. Here, we review the state of the field of using control theory approaches in computational psychiatry and show that recent research has mapped a neural control circuit consisting of frontal cortex, parietal cortex, and the cerebellum. This basic feedback control circuit is modulated by estimates of reward and cost via the basal ganglia as well as by arousal states coordinated by the insula, dorsal anterior cingulate cortex, amygdala, and locus coeruleus. One major approach within the broader field of control theory, known as proportion-integral-derivative (PID) control, has shown promise as a model of human behavior which enables precise and reliable estimates of underlying control parameters at the individual level. These control parameters correlate with self-reported fear and with both structural and functional variation in affect-related brain regions. This suggests that dysfunctional engagement of stress and arousal systems may suboptimally modulate parameters of domain-general goal-directed control algorithms, impairing performance in complex tasks involving movement, cognition, and affect. Future directions include clarifying the causal role of control deficits in stress- and anxiety-related disorders and developing clinically useful tools based on insights from control theory.

Converging Evidence for Frontopolar Cortex as a Target for Neuromodulation in Addiction Treatment.

Noninvasive brain stimulation technologies such as transcranial electrical and magnetic stimulation (tES and TMS) are emerging neuromodulation therapies that are being used to target the neural substrates of substance use disorders. By the end of 2022, 205 trials of tES or TMS in the treatment of substance use disorders had been published, with heterogeneous results, and there is still no consensus on the optimal target brain region. Recent work may help clarify where and how to apply stimulation, owing to expanding databases of neuroimaging studies, new systematic reviews, and improved methods for causal brain mapping. Whereas most previous clinical trials targeted the dorsolateral prefrontal cortex, accumulating data highlight the frontopolar cortex as a promising therapeutic target for transcranial brain stimulation in substance use disorders. This approach is supported by converging multimodal evidence, including lesion-based maps, functional MRI-based maps, tES studies, TMS studies, and dose-response relationships. This review highlights the importance of targeting the frontopolar area and tailoring the treatment according to interindividual variations in brain state and trait and electric field distribution patterns. This converging evidence supports the potential for treatment optimization through context, target, dose, and timing dimensions to improve clinical outcomes of transcranial brain stimulation in people with substance use disorders in future clinical trials.

Thalamo-cortical circuits associated with trait- and state-repetitive negative thinking in major depressive disorder.

BACKGROUND: Repetitive negative thinking (RNT), often referred to as rumination in the mood disorders literature, is a symptom dimension associated with poor prognosis and suicide in major depressive disorder (MDD). Given the transdiagnostic nature of RNT, this study aimed to evaluate the hypothesis that neurobiological substrates of RNT in MDD may share the brain mechanisms underlying obsessions, particularly those involving cortico-striatal-thalamic-cortical (CSTC) circuits. METHODS: Thirty-nine individuals with MDD underwent RNT induction during fMRI. Trait-RNT was measured by the Ruminative Response Scale (RRS) and state-RNT was measured by a visual analogue scale. We employed a connectome-wide association analysis examining the association between RNT intensity with striatal and thalamic connectivity. RESULTS: A greater RRS score was associated with hyperconnectivity of the right mediodorsal thalamus with prefrontal cortex, including lateral orbitofrontal cortex, along with Wernicke's area and posterior default mode network nodes (t = 4.66-6.70). A greater state-RNT score was associated with hyperconnectivity of the right laterodorsal thalamus with bilateral primary sensory and motor cortices, supplementary motor area, and Broca's area (t = 4.51-6.57). Unexpectedly, there were no significant findings related to the striatum. CONCLUSIONS: The present results suggest RNT in MDD is subserved by abnormal connectivity between right thalamic nuclei and cortical regions involved in both visceral and higher order cognitive processing. Emerging deep-brain neuromodulation methods may be useful to establish causal relationships between dysfunction of right thalamic-cortical circuits and RNT in MDD.

Neural correlates of negative life events and their relationships with alcohol and cannabis use initiation.

OBJECTIVE: Negative life events (NLEs), e.g., poor academic performance (controllable) or being the victim of a crime (uncontrollable), can profoundly affect the trajectory of one's life. Yet, their impact on how the brain develops is still not well understood. This investigation examined the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) dataset for the impact of NLEs on the initiation of alcohol and cannabis use, as well as underlying neural mechanisms. METHODS: This study evaluated the impact of controllable and uncontrollable NLEs on substance use initiation in 207 youth who initiated alcohol use, 168 who initiated cannabis use, and compared it to 128 youth who remained substance-naïve, using generalised linear regression models. Mediation analyses were conducted to determine neural pathways of NLE impacting substance use trajectories. RESULTS: Dose-response relationships between controllable NLEs and substance use initiation were observed. Having one controllable NLE increased the odds of alcohol initiation by 50% (95%CI [1.18, 1.93]) and cannabis initiation by 73% (95%CI [1.36, 2.24]), respectively. Greater cortical thickness in left banks of the superior temporal sulcus mediated effects of controllable NLEs on alcohol and cannabis initiations. Greater left caudate gray-matter volumes mediated effects of controllable NLEs on cannabis initiation. CONCLUSIONS: Controllable but not uncontrollable NLEs increased the odds of alcohol and cannabis initiation. Moreover, those individuals with less mature brain structures at the time of the NLEs experienced a greater impact of NLEs on subsequent initiation of alcohol or cannabis use. Targeting youth experiencing controllable NLEs may help mitigate alcohol and cannabis initiation.

Screen media activity in youth: A critical review of mental health and neuroscience findings.

This review has two primary objectives: (1) to offer a balanced examination of recent findings on the relationship between screen media activity (SMA) in young individuals and outcomes such as sleep patterns, mood disturbances, anxiety-related concerns, and cognitive processes; and (2) to introduce a novel multi-level system model that integrates these findings, resolves contradictions in the literature, and guides future studies in examining key covariates affecting the SMA-mental health relationship. Key findings include: (1) Several meta-analyses reveal a significant association between SMA and mental health issues, particularly anxiety and depression, including specific negative effects linked to prolonged screen time; (2) substantial evidence indicates that SMA has both immediate and long-term impacts on sleep duration and quality; (3) the relationship between SMA and cognitive functioning is complex, with mixed findings showing both positive and negative associations; and (4) the multifaceted relationship between SMA and various aspects of adolescent life is influenced by a wide range of environmental and contextual factors. SMA in youth is best understood within a complex system encompassing individual, caregiver, school, peer, and environmental factors, as framed by Bronfenbrenner's ecological systems theory, which identifies five interrelated systems (microsystem, mesosystem, exosystem, macrosystem, and chronosystem) that influence development across both proximal and distal levels of the environment. This model provides a framework for future research to examine these interactions, considering moderating factors, and to develop targeted interventions that can mitigate potential adverse effects of SMA on mental well-being.

Impaired eating behaviors but intact metabolic hormone levels in individuals with major depressive disorder and generalized anxiety disorder.

BACKGROUND: Major depressive disorder (MDD) and generalized anxiety disorder (GAD) contribute significantly to global health burdens. Identifying disease markers for these comorbid disorders can increase understanding of pathogenesis and improve screening and intervention strategies. This study examined the association of physical health factors with MDD and MDD + GAD, across sexes. METHODS: Two samples of participants from the Tulsa-1000 study (exploratory cohort: N = 136; confirmatory cohort: N = 185) completed body composition measurements, eating behavior (Three Factor Eating Questionnaire [TFEQ], Eating Disorder Diagnostic Scale [EDDS]), exercise questionnaires, and a blood draw. Metabolic hormone concentrations (leptin, insulin, and adiponectin) were analyzed from blood samples. Within each cohort, a two-way analysis of variance compared three groups (MDD, MDD + GAD, and healthy controls [HC]), sex, and their interaction on dependent variables. Hedges g was calculated to reflect effect size magnitude. RESULTS: Medium-to-large group main effects across cohorts indicated that compared to HC: (1) MDD (g = 1.71/0.57) and MDD + GAD (g = 0.93/0.69) reported higher TFEQ Disinhibition scores; (2) MDD endorsed higher TFEQ Hunger scores (g = 0.66/0.48); and (3) MDD (g = 1.60/1.30) and MDD + GAD (g = 0.92/1.72) reported greater EDDS scores. Large sex main effects across cohorts indicated that females exhibited higher levels than males for percent body fat (g = 1.07/1.17), leptin (g = 1.27/1.12), and adiponectin (g=0.82/0.88). LIMITATIONS: The power to detect group*sex interactions was limited due to a greater number of females (than males) in the study, and over half of clinical participants were taking medications. CONCLUSIONS: Individuals with MDD and MDD + GAD demonstrate difficulties in regulating eating behaviors, potentially contributing to functional impairment and increased disease burden.

The impact of floatation therapy on body image and anxiety in anorexia nervosa: a randomised clinical efficacy trial.

Background: Body image disturbance and anxiety are core features of anorexia nervosa (AN), a psychiatric disorder with one of the highest mortality rates. This study examined the efficacy of a novel non-pharmacological treatment, floatation-REST (Reduced Environmental Stimulation Therapy) on body image disturbance and anxiety in inpatients with AN. Methods: This parallel group randomised controlled trial compared floatation-REST vs. care as usual in women and girls hospitalised for treatment of AN in Tulsa, Oklahoma, USA. Participants were randomised on a 2:1 ratio to receive eight, twice-weekly, 60-min floatation-REST sessions for 4 weeks, in addition to care as usual, or to receive care as usual. The primary outcome was the average change in body dissatisfaction from pre- to post-float as measured by the Photographic Figure Rating Scale. The secondary outcome was the average change in anxiety from pre- to post-float as measured by the state version of the State Trait Anxiety Inventory. Longitudinal effects of floatation-REST on body dissatisfaction were also examined. All analyses were conducted using the intention-to-treat principle. Planned linear mixed models tested the effect of floatation-REST vs. care as usual. The trial was preregistered (clinicaltrials.govNCT03610451). Findings: Between March 16, 2018 and February 25, 2021, 133 participants were screened for eligibility, and 86 were consented. Eighteen were excluded after consent, for a final randomisation sample of 68 participants (45 floatation-REST; 23 care as usual). There were two session by condition interactions on body dissatisfaction (p = 0.00026) and state anxiety (p < 0.0001), such that the floatation-REST group exhibited acute (i.e., pre- to post-session) reductions in body dissatisfaction (floatation-REST group mean change (Δm) = -0.43; 95% CI -0.56 to -0.30, p < 0.0001, Cohen's d = 0.23), and acute reductions in anxiety (floatation-REST group Δm = -15.75; 95% CI -17.95 to -13.56, p < 0.0001, Cohen's d = 1.52); however, the care as usual group exhibited no significant changes. With regard to longitudinal results, there was a significant time by treatment interaction between baseline and immediately post intervention (p = 0.012) and baseline and six-month follow up (p = 0.0019). At immediately post intervention, there was a trending reduction in body dissatisfaction for the floatation-REST group (Δm = -0.41, 95% CI -0.86 to 0.03, p = 0.068) and care as usual group (Δm = 0.61; 95% CI -0.04 to 1.27, p = 0.070). At six-months post-intervention, the floatation-REST group exhibited lower body dissatisfaction (Δm = -0.91; 95% CI -1.37 to -0.45, p = 0.0020, Cohen's d = 0.53) whereas the care as usual group reported no change in body dissatisfaction (Δm = 0.35; 95% CI -0.28 to 0.98, p = 0.96) relative to baseline. There were no adverse events related to the trial during the study. Interpretation: Our findings suggest that Floatation-REST decreased body dissatisfaction compared to care as usual acutely after each float session and at six-month follow-up. Floatation-REST has potential utility for the treatment of body image disturbance and anxiety in AN. These results may be limited by some generalisability concerns given the recruitment of a modest sample receiving inpatient treatment at a single site. Funding: The William K. Warren Foundation.